Amgen’s AMG 811 Fails to Improve Lupus Outcomes in Phase 1 Trial

Patients with systemic lupus erythematosus (SLE) with or without lupus nephritis (LN) showed no clinical benefit when treated with Amgen‘s investigative anti-interferon-gamma antibody, AMG 811, in a Phase 1b  (NCT00818948) clinical trial.

Some indicators of the disease dropped in response to the treatment, but less so in LN patients.

The results of the clinical trial were reported in the article, “Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-γ monoclonal antibody, in SLE subjects without or with lupus nephritis,” published in the journal Lupus Science & Medicine.

Lupus nephritis (LN) is a form of kidney inflammation that occurs in patients with lupus. It is associated with high levels of a protein called interferon gamma (IFN-γ). Amgen’s AMG 811 was designed to target IFN-γ.

The study enrolled 56 patients ages 18 to 70 with lupus: 28 without LN and 28 with LN. Participants in the two groups received one of three different doses of AMG 811 or a placebo every four weeks for a total of three doses.

Clinical conditions of the study participants were assessed using the Safety of Estrogen in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index scores (SELENA-SLEDAI, a measure of ongoing disease activity in lupus).

However, AMG 811 had no effect on these scores.

A drop was seen in two indicators of IFN-γ activity. CXCL-10 protein levels and RNA IFN-γ blockade signatures (a score that reflects the impact of inhibiting IFN-γ on the activity of certain disease-related genes), dropped in the treated patients, compared with those who received the placebo. But this effect was not sustained in LN patients despite continued dosing.

“IFN-γ-associated biomarkers decreased with AMG 811; effects were less pronounced and not sustained in LN subjects,” the researchers wrote.

The overall safety profile of AMG 811 was found to be acceptable. Rates of adverse events in the treated and placebo arms were similar.

“This study provides a detailed characterization of the pharmacokinetic and pharmacodynamic profiles of multiple-dose administration of AMG 811 across a broad dose range in two clinically distinct SLE subpopulations,” researchers wrote.

“Given the small size of the study, no firm conclusions can be drawn about the clinical impact of AMG 811 in SLE; however, sufficiently overcoming the IFN-related abnormalities associated with LN, in particular, with targeted inhibition of the IFN-γ pathway to achieve a clinical impact may be challenging,” they added in the study.

“AMG 811 demonstrated favorable pharmacokinetics and acceptable safety profile, but no evidence of clinical impact,” the researchers concluded.

Amgen sponsored the clinical trial.